New information on the possible interaction between clopidogrel and proton pump inhibitors
22.03.2010
Having analysed the new data, the European Medicines Agency (EMA) published a press release on the possible interaction between clopidogrel and proton pump inhibitors.
Clopidogrel is an inhibitor of platelet aggregation, used to prevent blood clots in patients with myocardial infarct or stroke. In the human organism, clopidogrel converts into its active form with the help of the CYP2C19 enzyme. Proton pump inhibitors are used in prevention and treatment of dyspepsia and peptic ulcers. Since dyspepsia and peptic ulcers can occur as adverse reactions to the clopidogrel therapy, the patients taking clopidogrel often also take proton pump inhibitors in order to prevent or relieve the symptoms.
After publication of observational studies suggesting that proton pump inhibitors may reduce the effectiveness of clopidogrel by decreasing its conversion into its active form, in May 2009 the Committee for Medicinal Products for Human Use (CHMP) of the EMA recommended safety labeling revision of the product documentation for all medicines containing clopidogrel as active substance so as to include the information regarding the need to avoid their simultaneous use with proton pump inhibitors, unless absolutely necessary.
In the meantime, the Committee for Medicinal Products for Human Use of the EMA analysed the results of the new studies, some of which brought into question the clinical importance of interaction between proton pump inhibitors as a class of medicines and clopidogrel. The two studies completed at the end of August 2009 examined the effect of omeprazole on the blood level of the active metabolite of clopidogrel. The studies confirmed that omeprazole may decrease the blood level of the active metabolite of clopidogrel and diminish its anti-aggregating effects, thereby supporting the conclusion that there is interaction between clopidogrel and omeprazole or esomeprazole.
Taking into account all currently available data, the Committee for Medicinal Products for Human Use of the EMA and its Working Group on Pharmacovigilance concluded that there was no evidence which would warrant extending the warning to other proton pump inhibitors. The warning to avoid simultaneous use applies only to clopidogrel and omeprazole or esomeprazole. The Committee advised to include a description of results of the studies which revealed the interaction between clopidogrel and omeprazole into the product documentation for these medicinal products.
After the proposed revisions are accepted in the European Union, the relevant Summary of Product Characteristics and the Patient Information Leaflet approved in Croatia will be revised accordingly. The Agency for Medicinal Products and Medical Devices would like to stress the duty to report ADRs and will continue to monitor the safe use of this group of medicinal products.
The EMA's press release is available from the link below:
http://www.ema.europa.eu/humandocs/PDFs/EPAR/Plavix/17494810en.pdf
